Clinical Utility and Genomic Landscape of Comprehensive Genomic Profiling in Biliary Tract Tumors: A Single-Center Real-World Study.

Background

Comprehensive genomic profiling (CGP) is increasingly incorporated into the management of biliary tract tumors (BTTs); however, single-center real-world data integrating clinical utility and site-specific genomic landscape remain limited.

Methods

This retrospective single-center observational study included 91 patients with BTTs who underwent CGP. The primary endpoints were the rates of potentially actionable genomic alterations, expert panel-based therapeutic options, and implementation of genomically matched therapy. Secondary endpoints included the distribution of recurrent and clinically relevant genomic alterations according to the primary tumor site.

Results

The cohort included 46 patients with intrahepatic cholangiocarcinoma (iCCA), 19 with extrahepatic cholangiocarcinoma (eCCA), 24 with gallbladder cancer (GBC), and 2 with ampullary tumors. CGP was successfully performed in all 91 patients. Reportable genomic alterations were detected in 88 patients (96.7%), whereas no reportable alteration was detected in three patients (3.3%). The most frequently altered genes were TP53 (51/91, 56.0%), KRAS (21/91, 23.1%), CDKN2A (18/91, 19.8%), SMAD4 (14/91, 15.4%), and ARID1A/PBRM1 (12/91, 13.2%). Potentially actionable genomic alterations were identified in 21 patients (23.1%). Expert panel-based therapeutic options were identified in 15 patients (16.5%), and genomically matched therapy was introduced in 7 patients (7.7%). Matched therapy was introduced the most frequently in iCCA (6/46, 13%), followed by GBC (1/24, 4.2%), whereas no patient with eCCA or ampullary tumor received matched therapy.

Conclusions

CGP revealed a heterogeneous genomic landscape across BTT subtypes and provided clinically actionable information in a limited but meaningful subset of patients. The practical utility of CGP was the greatest in selected molecular subsets, particularly iCCA.